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General Overview 4/20/ A few drugs act by virtue of their physicochemical properties, e.g. laxative agent (MgSO 4 ), general anesthetics (based on its lipid solubility (?), osmotic diuretics (mannitol) Some drugs act as false substrates (sulphonamides) or inhibitor for certain transport systems (cardiac glycosides) or enzymes (NSAIDs) Most drugs produce their effects by acting on specific protein molecules, usually located in the cell membrane. These proteins are called receptors

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Receptor, Agonist & Antagonist 4/20/ Receptors normally respond to endogenous chemicals in the body. These chemicals are either synaptic transmitter substances (neurotransmitters) or hormones, for example acetylcholine, epinephrine, insulin, aldosterone etc. Chemicals or drugs that activate receptors and produce a response are called agonist. Drugs or chemicals that combine to receptors but do not activate them are called antagonist

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Receptors 4/20/ They are protein molecules which are normally activated by neurotransmitters or hormones. Many receptors have now been cloned and their amino acid sequences determined. The 4 main type of receptors are: 1. Agonist-gated receptors are made up from subunits which form a central ion channel (e.g. nicotinic receptor) 2. G-protein-coupled receptors form a family of receptors with seven membrane-spanning helices

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Drug-receptor Interactions 4/20/ The activation of receptors by an agonist is coupled to the physiological or biochemical responses by transduction mechanisms that often (but not always) involve molecules called second messengers (for example Ca 2+, inositol triphosphate, diacylglycerol and cAMP) The interaction between a drug and the binding site of the receptor depends on the complementary of “fit” of the 2 molecules. The closser the fit and the grater the number of bonds (usually non-covalent), the stronger will be the attractive forces between them, and the higher the affinity of the drug for the receptor.

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Specificity & selectivity 4/20/ The ability of a drug to combine with one particular type of receptor is called specificity. No drug is truly specific but many have a relatively selective action on one type of receptor. Drugs are prescribed to produce a therapeutic effect but they often produce additional unwanted effects which range from the trivial (slight nausea) to the fatal (aplastic anaemia)

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Neurotransmitters 4/20/ Neurotransmitter substances are chemicals released from nerve terminals which diffuse across the synaptic cleft and bind to the receptors. The neurotransmitter activates receptors, presumably by changing their conformation, and triggers a sequences of post-synaptic events resulting in, for example, muscle contraction or glandular secretion. Following its release, the transmitter is inactivated by either degradation (e.g. acetylcholine) or reuptake (e.g. norepinephrine, GABA). Many drugs act by either reducing or enhancing synaptic tranmission.

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Hormones 4/20/ Hormones are chemicals released into bloodstream; they produce their physiological effects on tissues possessing the necessary specific hormone receptors. Drugs may interact with the endocrine system by inhibiting (e.g. antithyroid drugs) or increasing (e.g. oral antidiabetic agents) hormone release. Other drugs interact with hormone receptors which may be activated (e.g. steroidal anti-inflammatory drugs) or blocked (e.g. oestrogen antagonists). Local hormones (autacoids) such as histamine, serotonin (5-HT), kinins and prostaglandins are released in pathological processes.